Antimicrobial surfaces have been a major challenge particularly in medicine where microbial agents tend to accumulate and propagate onto implantable devices made of various materials, particularly onto polymers. For example, indwelling catheters have to be removed sometimes shortly after administration due to accumulation of bacteria. For orthopedic implants such as artificial hips accumulation of bacteria may result in severe infection shortly or a few months after implant which in turn necessitates the removal of the implant an administration of high dose of antibacterial agents for healing before re-implantation. Urinary catheters may also result in a bladder infection from bacteria tracking through the catheter. Dental restoration material tend also to accumulate bacteria which result is deterioration of the restoration material while infecting the neighboring soft and hard tissues including the gums and dentin.
A number of reports describe experiments in which an antibacterial agent was incorporated into materials in order to inhibit bacterial growth. However, the antibacterial activity of these materials was found to be dependent upon release of the antibacterial agents into the surrounding milieu by various releasing rates.
U.S. Pat. No. 5,980,868 to Homola et al, describes dental coating of PEI reacted with a monolayer of fatty acid molecules, which fatty acids bond to the PEI layers with through their carboxylic groups. The invented material is said to be applied to dental surfaces by dental applicators including dental floss, tape, swabs and sticks. Published PCT Application No. WO 93/20775 introduces dental coating materials that contain particles of poly(fluoroetylene) coated with polyethyleneimine.
It has been reported that polycations possess antibacterial properties by interacting with and disrupting bacterial cell membranes. A number of polymers that exhibit antibacterial properties were developed for this purpose including soluble and insoluble pyridinium-type polymers which are involved in surface coating, azidated poly(vinyl chloride) which can be used to prevent bacterial adhesion of medical devices, PEG polymers that can be modified on polyurethane surfaces and also prevent initial adhesion bacteria to the biomaterial surfaces, and chitosans-polyethyleneimine that exhibit antibacterial and antifungal activity.
Numerous publications have demonstrated the utility of cationic polymers with quaternary ammonium groups as antimicrobial compounds. For example, U.S. Pat. No. 6,559,116 to Godfroid discloses antimicrobial composition for hard surface cleaning which consists of cationic antimicrobial active component which includes alkyltrimethylammonium halides and nitrogen-containing polymers such as polyethyleneimine. Lin et al (Lin J, Qiu S, Lewis K, Klibanov M. Bacterial properties of flat surfaces and nanoparticles derivatized with alkylated polyethylenimines. Biotechnol Prog 2002; 18:1082-1086) determined that covalently coated surfaces with N-alkylated poly(ethyleneimine) (PEI) may be effective against some airborne or waterborne Gram-positive and Gram-negative bacteria. Magnetoferic (Fe3O4) nanoparticles containing NH2 groups and derivatized with alkylated polyethylenimines possess also antibacterial properties. The antibacterial activity was dependant on molecular weight of the conjugate. The results showed for example that N-alkylated PEI of 2 and 0.8 kDa had a weak bactericidal activity. High activity of polycationic agents, on the other hand, may be achieved by 750-25 kDa N-alkylated PEI.
The antibacterial action is suggested to result from absorption of positively charged polymers onto negatively charged cell surfaces of the bacteria. This process was thought to be responsible for the increase of cell permeability and disruption of cell membranes. (Kawabata N, Nishiguchi M. Antibacterial activity of soluble pyridinium-type polymers. Appl Environ Microbiol 1988; 54:2532-2535)
U.S. Pat. Nos. 5,733,949, 5,408,022, and 5,494,987 to Imazato et al disclose compositions comprising three polymerizable vinyl based monomers having a group with antimicrobial activity, a carboxylic acid group and a monomer having an hydroxyl group. The composition may possess effective antimicrobial activity due to the penetration properties of the carboxylic acid and hydroxyl groups into the bacteria cell. According to these patents the activity is declining after one month with the active compound leaching to the surroundings.
Imazato et al, (J. Dentisty 28. 2000, 61-67), discloses the use of 12-methacycloyloxydodecylpyridinium bromide (MDPB) as monomer in acrylate dental primers. In the course of the study it was found that the monomer does not contribute to the cytotoxicity to human pulpal cells. In an another article, (Eur. J. Oral Sci. 110, 2002, 168-174) Imazato reports on the use of three dentine-bonding agents containing MDPB for treating bacterial infections of the artificial root carries lesions and found it effective when incorporated as monomer in the bonding composition. Yet in another article (Biomaterials, 24. 2003, 3605-9) grinded polymerized MDPB exhibited strong anti S. mutans activity. In the study it was also found that unpolymerized monomer leach out from the grinded polymerized MDPB.
U.S. Pat. No. 5,798,117 to New at al. discloses surfaces having phosphatidyl choline (O—POO—CH2—CH2—N—R3) derivatives capable of acting as antimicrobial surface. Similarly, U.S. Pat. No. 6,562,330 discloses certain compositions of antimicrobial materials based on zwiterioic functional groups such as phosphatidyl choline (O—POO—CH2—CH2—N—R3) derivatives, amino acid derivatives and the like.